1,1'-Carbonyldiimidazole → Benzyl 2-benzamido-7a-(5-bromo-2-fluoro-phenyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylate

HRID 77575Notes

Reaction equation

HRID 77575 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([NH:21][C:22]([NH:24][C:25]1([C:42]2[CH:47]=[C:46]([Br:48])[CH:45]=[CH:44][C:43]=2[F:49])[CH:29]([CH2:30]O)[CH2:28][N:27]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[CH2:26]1)=[S:23])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O1CCCC1.O>[C:13]([NH:21][C:22]1[S:23][CH2:30][CH:29]2[CH2:28][N:27]([C:32]([O:34][CH2:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:33])[CH2:26][C:25]2([C:42]2[CH:47]=[C:46]([Br:48])[CH:45]=[CH:44][C:43]=2[F:49])[N:24]=1)(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86762756Benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 86762759Benzyl 2-benzamido-7a-(5-bromo-2-fluoro-phenyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylateYield 58.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1,1′-carbonyldiimidazole (2.87 g, 17.7 mmol) is added to a solution of benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate (5.198 g, 8.86 mmol) in tetrahydrofuran (52 mL). The mixture is stirred for 1.5 hours at room temperature and then the reaction is heated at reflux overnight under nitrogen. The reaction is cooled, diluted with water, and extracted with ethyl acetate (3×). The organic layers are combined, dried over sodium sulfate, filtered, and the solvent removed in vacuo. The crude product is purified over silica gel with a 30 minute 5% to 100% EtOAc in hexanes gradient to give the title compound (2.93 g, 58%). ES/MS (m/e): (79Br/81Br). 568/570 (M+H)

Workup

  1. temperaturethe reaction is heated
  2. temperatureat reflux overnight under nitrogen
  3. temperatureThe reaction is cooled
  4. extractionextracted with ethyl acetate (3×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe crude product is purified over silica gel with a 30 minute 5% to 100% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-0fc2aa990d3941e19e51e9190dd65ee4
Source dataset
uspto-grants-2014_09
Patent number
US08841293B1

Reaction notes

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